Chemoprevention of indirect and direct chemical carcinogenesis by carotenoids as oxygen radical quenchers.

Beta-carotene (BC) and canthaxanthine (CX), two carotenoids with and without pro-vitamin A activity, respectively, were found to help to prevent benzo[a]pyrene (BP)-induced skin carcinogenesis in the dark and BP photocarcinogenesis (UV 300-400 nm) when given as an oral supplement to female Swiss albino mice. The same experimental procedure was adapted to 8-methoxypsoralen (8-MOP) photoinduction of mammary carcinomas in mice. Here also, the two carotenoids were strongly antitumorigenic. Indeed, 8-MOP photomutagenesis, tested in S. typhimurium TA 102, appeared to depend on a two-step reaction, namely an oxygen-independent DNA-8-MOP photoadduct, followed by an oxygen-dependent second step, sensitive to carotenoids. This result suggests that dietary carotenoids (powerful antioxidant molecules) might prevent the carcinogenic risk caused by substances that are transformed into ultimate carcinogens by oxidative processes which are indirectly carcinogenic. Finally, to verify whether supplemental carotenoids can affect carcinogenesis where neither light excitation nor oxidative metabolic processes are involved, an experimental attempt was made on gastric carcinogenesis induced in rats by the direct carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The results demonstrate that supplemental carotenoids do not affect initiation and progression stages, but do prevent the progression stage of dysplasias to infiltrating gastric carcinomas. Thus, this provides strong presumptive evidence for oxygen radical involvement in the later stages of this neoplastic development, as recently reported in the literature. As far as mutagenicity in S. typhimurium is concerned, carotenoids do not exert, as expected, any protective effect on MNNG mutagenic activity. The above experimental data suggest that supplemental carotenoids, instead of sunscreen preparations, can be adopted by outdoor workers to prevent skin cancer. Accordingly, such natural antioxidants may be useful in human chemoprevention against neoplasias of the lung, breast, urinary bladder, and colon and rectum even after radical surgery.

Human lymphocyte micronucleus genotoxicity test with mixtures of phytochemicals in environmental concentrations.

This study was carried out to assess the genotoxicity of mixtures of pesticides using the micronucleus test with human lymphocytes in culture. Benomyl, azinphos-methyl, diazinon, dimethoate, pirimiphos-methyl pesticides were tested at doses estimated from their daily intake (EDI). Benomyl is a carbamate fungicide, the other compounds are organophosphorous insecticides. The compounds were tested both separately and in combination. The results showed a weak genotoxicity for three of the four organophosphorous insecticides and for benomyl. The various mixtures did not give additive effects.

beta-Carotene storage in rat organs following carrier mediated supplementation.

One rat group was supplemented with beta-carotene (BC) both in beadlets and the crystalline form in arachidic oil as a carrier added to standard diet; another rat group was given 1 ml crystalline BC-arachidic oil by gavage twice a week. In both rat groups, each rat ingested 350 mg BC/week for 12 weeks. The animals were then sacrificed and BC levels together with retinyl palmitate presence were assessed by HPLC analysis in liver, lung, kidney, small intestine, mesenteric fat, brain, spleen, stomach and blood plasma. In the first group, high BC storage, ranging from 4.2 to 45.2 nmols/g wet tissue, was found in liver, small intestine, spleen; lesser BC levels were found in lung, kidney, stomach, blood serum; retinyl palmitate was found in liver and lung. In the second group BC levels ranging from 0.5 up to 5,763 nmols/g wet tissue were detected in all organs, except for brain and stomach; the highest levels were in the lung; retinyl palmitate was detected in liver. The lung appeared to be a target organ for BC, as confirmed by its presence in the lungs of control rats fed standard diet and given 1 ml of arachidic oil alone by gavage twice a week.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypothalamo-hypophyseal metastasis: a rare initial manifestation of adenocarcinoma of the jejunum. Description of a clinical case]. / Metastasi ipotalamo-ipofisaria: rara manifestazione iniziale di adenocarcinoma del digiuno. Descrizione di un caso clinico.

A rare case of jejunal adenocarcinoma is described in which the initial clinical sign was diabetes insipidus and hypopituitarism linked to hypothalamohypophyseal metastasis. The rarity of the intestinal neoplasm and the unusual site of the metastatic lesions are underlined.

[Variations in the enzymatic activity in the calf muscle of the rat following ischemia]. / Variazioni di attività enzimatiche in muscolo surale di ratto in seguito ad ischemia.

Muscle lesions induced by ischaemia have been investigated in depth from the morphological standpoint, though the metabolic changes thus caused are still the subjects of discussion. Measurements were therefore made of enzyme activities in rat calf muscle, and their changes following incomplete ischaemia. Three enzymes were studied: CPK (typical of muscle metabolism), G-6-PDH (pentose cycle, indicator of the extent of repair processes), and uptake of a labelled amino acid (L-leucine, on the part of tissue proteins. An initial increase in activity and uptake was followed by recovery functions, due to installation of a collateral circulation. This appeared to be complete by the 5th day.

Dietary carotenoids block photocarcinogenic enhancement by benzo (a)pyrene and inhibit its carcinogenesis in the dark.

The carotenoids beta-carotene (C) and canthaxanthine (CX), with and without pro-vitamin A activity, respectively, when perorally administered to mice, markedly prevent benzo(a)pyrene photocarcinogenic enhancement (BP-PCE), continue to block such BP-PCE and protect significantly against BP carcinogenesis in mice maintained in the dark. These results appear relevant to both the pathogenesis of chemical carcinogenesis and rational programs of skin cancer prevention in humans.

Photocarcinogenesis by methoxypsoralen, neutral red, proflavine, and long UV radiation.

A study of the photosensitizing effects of 8-methoxypsoralen (MOP), neutral red (NR), and proflavine (PF) on the skin of female Swiss albino mice, strain 955, was carried out using fractionated exposure to long ultraviolet light (300-400 nm) and visible light (tungsten emission). The results (1) confirmed MOP photocarcinogenicity, (2) demonstrated that both NR and PF are photocarcinogens, and, further, (3) showed that the above UV light with 2.6% of fluence at 313 nm is a long-term carcinogenic agent even though the total dose of 313 nm was 100 times less than the minimal UV tumorigenic dose in mice. The tumors were mammary adenocarcinomas, carcinomas of skin appendages, carcino-mixo-sarcomas, lymphomas, and one case of thyroid adenocarcinoma. The implications of the above data regarding the controversy about oncogenic risks in photochemotherapy are discussed.